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The present invention provides information technology based techniques including computer software in therapeutics or drug discovery. In an exemplary embodiment, the present invention provides software for determining information about properties of substances based upon information about structures of living, fixed or non-living cells, or cell fractions. Computer code according to the present invention enable researchers and scientists to identify promising candidates in the search for new and better medicines and medical techniques.
For a long time, researchers in the pharmaceutical field have sought for better ways of searching for substances possessing properties which make them suitable as medicines. In the early days, researches generally relied upon dyes, or extracts from plants, or microbiological broths for such substances. Examples of such substances include aspirin, and antibiotics.
Substances having desirable bio-active properties, however, are often difficult to isolate and identify. Advances in organic chemistry such as rapid chemical synthesis techniques have increased the number of compounds that researchers want to test for biological activity. Conventionally, substances were often tested on humans or animal subjects to determine biological activity. While results from such tests can be highly predictive, these types of tests can be time consuming, limiting the progress of the testing.
There have been some attempts to use image acquisition techniques to screen for large numbers of molecules based upon cell information. Conventional image acquisition systems exist that generally capture digitized images of discrete cells for identification purposes. Identification often occurs during the image capturing step, which is limiting. In most cases, these conventional techniques cannot comprehensively provide for complete cellular information but can only be used to identify a fairly limited set of information.
What is needed are techniques for collecting and managing information useful in finding the effects of manipulations on cell function, response or behavior.
According to the present invention, techniques for using information technology in therapeutics or drug discovery. In an exemplary embodiment, computer software for determining information about the properties of substances based upon information about a structure or the morphology of living, fixed or dead cells (e.g., elements, cell portions and cell fractions) exposed to substances are provided. Computer software according to the present invention enables researchers and/or scientists to identify promising candidates in the search for new and better medicines or treatments using, for example, a cellular informatics database.
According to the present invention, a computer program for identification and verification of biological properties of substances can include code that administers a sample of the substance to a cell. The code determines one or more features for two or more cell components, or markers, in the presence of the substance. The code can form one or more descriptors from the features. Descriptors can be formed by combining features of two or more cell components as identified using the markers. The code can then search one or more descriptors obtained from prior administered substances upon cells in order to locate descriptors having a relationship to the descriptors noted for the substance under study. The code predicts properties of the administered substance based upon the properties of the prior administered substances using the relationship between the descriptors. The code can provide for identifying properties of substances based upon effects on cell characteristics. Candidate drug mechanisms of action, potency, specificity, pharmacodynamic, and pharmacokinetic parameters, toxicity, and the like can be used as substance properties.
In another embodiment according to the present invention, computer programs for animal model selection, clinical trial design and patient management can be provided.
In a further embodiment according to the present invention, techniques for using cellular information in predictive methods for acquiring, analyzing and interpreting cellular data are incorporated into a computer program product including code. In one such embodiment, code for predicting properties of an unknown substance based upon information about effects of one or more known substances on a cell population is provided. The code performs a variety of tasks, such as populating a database with descriptors of cells subjected to known substances. Such descriptors can be determined from imaging the cell population. However, in some embodiments, descriptors can be derived by measurements and combinations of measurements and the like. The code determines descriptors for the unknown substance from imaging a second cell population. The second cell population has been treated with the unknown substance. Then, the code can determine a relationship between the descriptors determined from the unknown substance with the descriptors determined from the known substance. From this relationship, an inference can be made about the unknown substance.
In a yet further embodiment according to the present invention, a computer program for determining properties of a manipulation based upon effects of the manipulation on one or more cell fractions. The computer program includes code that can provide the manipulation to the cell fractions. The code can also determine one or more features of markers corresponding to cell components within the cell fractions in the presence of the manipulation. Code for forming descriptors from the features is also included. Code for searching in a database in order to locate descriptors based upon at least one of the descriptors obtained from the manipulation is also included. The computer program can include code for determining, based upon the descriptors located in the database, properties of the manipulation.
Moreover, the present invention provides computer software for mapping a manipulation of cells based upon a morphological characteristic. The computer software includes code for providing a plurality of cells, e.g., dead, live, cell fragments, cell components, cell substructures. The software also includes code for manipulating the plurality of cells, where manipulation occurs using a source(s) from one or a combination selected from an electrical source, a chemical source, a thermal source, a gravitational source, a nuclear source, a temporal source, and a biological source. The software code captures a morphological value from the plurality of cells. The morphological value can include one or any combination of characteristics such as a cell count, an area, a perimeter, a length, a breadth, a fiber length, a fiber breadth, a shape factor, an elliptical form factor, an inner radius, an outer radius, a mean radius, an equivalent radius, an equivalent sphere volume, an equivalent prolate volume, an equivalent oblate volume, an equivalent sphere surface area, an average gray value, a total gray value, and an optical density. The software code also assigns a degree of presence of the morphological value, and stores the morphological value from the plurality of cells. These values can be used for a statistical analysis to produce a statistical profile.
Still further, the present invention provides a computer program product for populating a database with manipulated biological information, e.g., cellular enzymatic activities, cellular cascades, cellular promoters, transcription factors, translation factors, cell cycle stage and apoptosis. The computer program product includes code for providing a plurality of cells in various stages of the cell cycle, where the stages of the cell cycle may include at least one selected from interphase, G0 phase, G1 phase, S phase, G2 phase, M phase which itself includes prophase, prometaphase, metaphase, anaphase, and telophase. The computer program also includes code for manipulating each of the cells in the various stages of the cell cycle. The computer program includes code for capturing (e.g., image acquisition) an image of the plurality of manipulated cells where the code for capturing provides a morphometric characteristic of the manipulated cells. The computer program product also includes code for populating a database with the morphometric characteristic of the plurality of manipulated cells. Accordingly, the present invention provides software for populating a database, which can be queried.
Numerous benefits are achieved by way of the present invention over conventional techniques. The present invention can provide techniques for predictive cellular bioinformatics that can stream line a number of important decisions made in the drug discovery industry, medical diagnostics and biological research. The present invention can be implemented on conventional hardware including databases. In other aspects, the present invention can find useful information about substances as well as cells or portions of cells, especially morphology. Embodiments can provide a holistic approach to cell based drug discovery that enables the understanding of properties of substances based on their overall effects on cell biology. The properties include, among others, clinical uses and descriptors, human and veterinary diagnostic uses and tests, or human and veterinary prognostic uses and tests. Depending upon the embodiment, one or more of these advantages may be present. These and other benefits are described throughout the present specification.